INTEGRATIVE REFLEX DYNAMICS IN RESPIRATORY CYCLE CONTROL

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This proposal addresses the hypothesis that respiratory variability is due to an 'instability' in mechanisms for the control of end-expiratory volume (EEV) in animals with compliant chest walls. This 'instability' is a form of complex irregular behavior in the nonlinear dynamics sense. We hypothesize that it is due to interactions of time-varying nonlinear pulmonary mechanoreceptor feedback with integrative central mechanisms for respiratory rhythm and pattern formation. We have described how the sensitivity of respiratory phase transitions to vagal afferent activity causes a variable breathing pattern. This effect is accentuated during lung deflation by continuous negative airway pressure (CNAP) and may be due partly to deflation-sensitive, slowly-adapting pulmonary receptors (DSARS). The present proposal studies intact upper airways to investigate the interactions of the above mechanisms (which control EEV by altering dynamics of respiratory phase transitions) with other mechanisms which control EEV by modulating upper airway expiratory activity. Because both groups of mechanisms are modulated by pulmonary mechanoreceptor feedback, we hypothesize that their interactions will increase the variability of the breathing pattern and may adversely impact gas exchange. additionally we will assess how chemical drive affects these mechanisms. We will also characterize DSARs, comparing them with pulmonary stretch and rapidly-adapting receptors and identifying some of their central projections. The proposed studies will extend current concepts about reflex control of respiratory pattern by examining the breath to breath reproducibility of vagally-mediated reflex effects and elucidating some mechanisms which are expected to impair this reproducibility. Furthermore, analogies with respiratory behavior in human neonates suggest broader applicability of the expected findings.